title: Angiotensin type 1 receptor inhibition enhances the extinction of fear memory.
abstract: BACKGROUND
  The current effective treatment options for posttraumatic stress disorder (PTSD) are limited, and therefore the need to explore new treatment strategies is critical. Pharmacological inhibition of the renin-angiotensin system is a common approach to treat hypertension, and emerging evidence highlights the importance of this pathway in stress and anxiety. A recent clinical study from our laboratory provides evidence supporting a role for the renin-angiotensin system in the regulation of the stress response in patients diagnosed with PTSD.
  
  
  METHODS
  With an animal model of PTSD and the selective angiotensin receptor type 1 (AT1) antagonist losartan, we investigated the acute and long-term effects of AT1 receptor inhibition on fear memory and baseline anxiety. After losartan treatment, we performed classical Pavlovian fear conditioning pairing auditory cues with footshocks and examined extinction behavior, gene expression changes in the brain, as well as neuroendocrine and cardiovascular responses.
  
  
  RESULTS
  After cued fear conditioning, both acute and 2-week administration of losartan enhanced the consolidation of extinction memory but had no effect on fear acquisition, baseline anxiety, blood pressure, and neuroendocrine stress measures. Gene expression changes in the brain were also altered in mice treated with losartan for 2 weeks, in particular reduced amygdala AT1 receptor and bed nucleus of the stria terminalis c-Fos messenger RNA levels.
  
  
  CONCLUSIONS
  These data suggest that AT1 receptor antagonism enhances the extinction of fear memory and therefore might be a beneficial therapy for PTSD patients who have impairments in extinction of aversive memories.
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Department of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom. Electronic address: pmarvar@emory.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Marvar
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Jared
authors.initials: J
authors.lastname: Goodman
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Choi
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Sunayana
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan
keywords: Angiotensin receptor type 1 (AT(1)); PTSD; cardiovascular disease; fear memory; renin-angiotensin; stress